Multiple NTS Neuron Populations Synergistically Suppress Physiologic Food Intake but are Dispensable for the Response to VSG

Several discrete groups of feeding-regulated neurons in the nucleus tractus solitarius (NTS) suppress food intake, including aversion-promoting neurons that express Cck (NTS ^Cck cells) and distinct Lepr - and Calcr -expressing neurons (NTS ^Lepr and NTS ^Calcr cells, respectively) that suppress food intake without promoting aversion. To test synergies among these cell groups we manipulated multiple NTS cell populations simultaneously. We found that activating multiple sets of NTS neurons (e.g., NTS ^Lepr plus NTS ^Calcr (NTS ^LC ), or NTS ^LC plus NTS ^Cck (NTS ^LCK )) suppressed feeding more robustly than activating single populations. While activating groups of cells that include NTS ^Cck neurons promoted conditioned taste avoidance (CTA), NTS ^LC activation produced no CTA despite abrogating feeding. Thus, the ability to promote CTA formation represents a dominant effect, but activating multiple non-aversive populations additively suppresses food intake without provoking aversion. Although silencing multiple NTS neuron groups augmented food intake and body weight more dramatically than silencing single populations, feeding activated many non-NTS ^LCK neurons and silencing NTS ^LCK neurons failed to blunt the weight loss response to vertical sleeve gastrectomy (VSG). Hence, while each of these NTS neuron populations plays crucial and additive roles in the control of energy balance, as-yet undefined cell types must make additional contributions to the control of feeding and the response to VSG.